Systemic sclerosis pathogenesis and emerging therapies. Yesassociated proteintafazzin yaptaz are transcriptional coactivators previously demonstrated to be involved in cellular stretch biology, and form the principal effector molecules of the hippo signalling pathway. Vitamin d vitd status also impacts function of most cell types and likely influences pathogenesis and clinical features of ssc. Recent findings regarding the participation and interaction of the innate and acquired immune system have led to a better understanding of the pathogenesis of the disease and to. There are two major subgroups of systemic sclerosis based on the extent of skin involvement. Classification, subsets and pathogenesis article pdf available in the journal of rheumatology 152. The fibrosis is caused by the bodys production of too much collagen, which normally strengthens and supports connective tissues. Similar to a healthy and functional society, the human body is dependent on each. Systemic sclerosis is a connective tissue disease of unknown aetiology characterised by autoimmunity, inflammation, vascular abnormalities and ultimately fibrosis. The pathological events in ssc may include impaired communication. Progressive systemic sclerosis pss is a condition associated with thickening of the skin and tethering to subcutaneous tissues as well as smooth muscle atrophy and fibrosis of internal organs such as the gastrointestinal tract, lungs, heart. It is characterized by the buildup of scar tissue fibrosis in the skin and other organs.
Pathogenesis of systemic sclerosis associated interstitial. Systemic sclerosis is a rare chronic disease of unknown cause characterized by diffuse fibrosis and vascular abnormalities in the skin, joints, and internal organs especially the esophagus, lower gi tract, lungs, heart, and kidneys. Systemic sclerosis, also called scleroderma, is an immunemediated rheumatic disease that is characterised by fibrosis of the skin and internal organs and vasculopathy. Systemic sclerosis is a complex autoimmune disease characterized by a chronic and frequently progressive course and by extensive patienttopatient variability. Environmental factors include exposure to the following. Systemic scleroderma is an autoimmune disorder that affects the skin and internal organs. Fibroblast abnormalities in the pathogenesis of systemic sclerosis. Although its pathogenesis is not fully understood, recent studies have advanced our knowledge on ssc. Key difference multiple sclerosis vs systemic sclerosis both multiple sclerosis and systemic sclerosis are autoimmune diseases whose pathogenesis is triggered by undiscovered environmental and genetic factors. Pathogenesis of interstitial lung disease, a major cause of death in systemic sclerosis, reflects the intrinsic disease pathobiology and is associated with distinct clinical phenotypes and laboratory characteristics. There have been advances in understanding of pathogenesis that reflect the interplay between immuneinflammatory processes and vasculopathy and fibrosis.
The b cells in ssc are constitutively activated and lead to the production of a plethora of. Systemic sclerosis is the most severe disease within the scleroderma spectrum and is a major medical challenge with high mortality and morbidity. Advances in pathogenesis and treatment of systemic sclerosis. Systemic sclerosis scleroderma leads to morbidity and mortality through a combination of inflammation, fibrosis and vascular damage leading to internal organ complications affecting the heart, lung, kidneys and bowel. Systemic sclerosis ssc is a complex, heterogeneous connective tissue disease ctd, characterized by immune abnormalities, microvasculopathy with capillary loss and excessive extracellular deposition with subsequent fibrosis of the skin and internal organs 1. Leris pleonosteosis, a congenital rheumatic disease, results from microduplication at 8q22. Improved understanding of systemic sclerosis has allowed better management of the disease, including improved classification and. This disease is also associated with certain susceptibility genes. Current frontiers in systemic sclerosis pathogenesis.
It can be regarded as a disease of connective tissue repair and this. The cardinal pathological features of ssc are autoimmunity, vasculopathy, and fibrosis. Recent studies revealed that periostin serves as a critical. Endothelial cell injury is an early and probably initiating event, but the precise aetiology remains unclear. Recent advances in understanding the pathogenic mechanisms have led to development of targetoriented and vasomodulatory drugs which play a pivotal role in treating various dermatological manifestations. Systemic sclerosis systemic scleroderma is a chronic connective tissue disease of unknown etiology that causes wide spread microvascular damage. This occurs in about 90 percent of patients with systemic sclerosis. Following the molecular pathways toward an understanding of the pathogenesis of systemic sclerosis sergio a. The commonest histological pattern of systemic sclerosisinterstitial lung disease is nonspecific interstitial pneumonia. Leris pleonosteosis, a congenital rheumatic disease.
It is a rare condition that affects mostly young and middleaged women, resulting in disproportionate morbidity and mortality. Pdf pathogenesis of systemic sclerosis researchgate. Current treatments focus on broad spectrum immunosuppression or organbased therapy for. Increased serum calpain activity is associated with hmgb1. Systemic sclerosis ssc is an intractable multifaceted disease with high mortality. Immune activation, vascular damage, and excessive synthesis of extracellular matrix with deposition of increased amounts of structurally normal collagen are all known to be important in the development of this illness 1,2. Difference between multiple sclerosis and systemic sclerosis. The disease can be either localized to the skin or involve other organs in addition to the skin. Angiogenesis dysregulation in the pathogenesis of systemic. Acreular classification criteria for sclerosis ssc. Topel, in textbook of clinical neurology third edition, 2007. The contribution of epigenetics to the pathogenesis and. Novel insights in the pathogenesis of systemic sclerosis.
Systemic sclerosis scleroderma, like other chronic diseases, is the consequence of a disruption of normal body functions. The human body works by an incredibly complex array of biological interactions that are delicately balanced and closely linked. Pathogenesis of human systemic lupus erythematosus. Systemic sclerosis ssc is an idiopathic autoimmune disease, that is, characterised by inflammation, cytokine imbalances and vasculopathy that leads to skin and lung fibrosis. The aetiology of ssc is currently an expanding area of study, since the exact nature of the events underlying this disease remains unclear. Ssc may be initiated in the vasculature, with evidence suggesting that some morphological changes may be apparent before disease onset. This means its a condition in which the immune system attacks the body. Systemic sclerosis is a complex autoimmune disease characterized by vasculopathy, fibrosis, and immune activation. Scleroderma is a group of autoimmune diseases that may result in changes to the skin, blood vessels, muscles, and internal organs. Systemic sclerosis is an autoimmunologic disease, but the pathogenesis is only partially understood. Certain factors are well known to trigger occurrence of the disease or create a similar clinical appearance. Interleukin33 il33, a member of the il1 superfamily, functions as a traditional cytokine and nuclear factor. Periostin is one of the matricellular proteins, a class of ecmrelated molecules defined by their ability to modulate cellmatrix interactions.
Systemic sclerosis ssc is a chronic, multisystem connective tissue disease with protean clinical manifestations. Systemic sclerosis, interstitial lung disease, calpain, hmgb1, microarray analysis background systemic sclerosis ssc or scleroderma is an intractable autoimmune disorder characterized by vasculopathy and fibrosis of the skin and visceral organs including the heart, kidney, and lung, which has high mortality and re. Although systemic sclerosis is uncommon, it has a high morbidity and mortality. Ssc is divided into diffuse cutaneous dcssc and limited cutaneous lcssc forms based on the extent of skin involvement. Multiple sclerosis is a chronic autoimmune, tcell mediated inflammatory disease affecting the central nervous system whereas systemic. Sscild most commonly occurs within 10 years of diagnosis, and may be seen in patients with either the limited or. Recent advances in understanding the pathogenesis of. Systemic sclerosis 2nd edition johns hopkins scleroderma. Individual papers have commented on or measured differing aspects of this abnormal rheology, including elevated whole. The factors responsible for maintaining persistent organ fibrosis in systemic sclerosis ssc are not known but emerging evidence implicates tolllike receptors tlrs in the pathogenesis of ssc.
The peak incidence of the disease is found between the third and fifth decade of life. The pathogenesis of ssc is complex and appears to involve endothelium, epithelium, fibroblasts and immunological mediators, resulting in dysregulated vascular remodelling and, ultimately, vasculopathy. Pathogenesis of systemic sclerosiscurrent concept and. Two major clinical subtypes are the limited and diffuse forms. Increased periostin levels in patients with systemic sclerosis.
Systemic scleroderma, or systemic sclerosis, is an autoimmune rheumatic disease characterised by excessive production and accumulation of collagen, called fibrosis, in the skin and internal organs and by injuries to small arteries. Systemic sclerosisassociated interstitial lung disease. Pathogenesis of systemic sclerosis scleroderma uptodate. Disease pathogenesis abstract systemic sclerosis ssc is a systemic autoimmune condition of unknown cause. Heartburn and other esophagus problems particularly trouble swallowing foods. Systemic sclerosis ssc results in significant morbidity and mortality due to organ fibrosis characterized by increased deposition of extracellular matrix ecm. Frontiers pathogenesis of systemic sclerosis immunology. Systemic sclerosis is a chronic autoimmune connective tissue disease characterized by vascular injury and fibrosis and by an impaired angiogenesis which cannot ensure an efficient vascular recovery. Systemic sclerosis ssc is an autoimmune systemic disease characterized by small vessel involvement that leads to tissue ischemia and fibroblast stimulation resulting in accumulation of collagen fibrosis in the skin and internal organs.
Comprised of the authoritative work of international experts, this fullyupdated second edition of scleroderma builds upon the wellregarded approach in the first edition to provide integrated, concise, and uptodate synthesis of current concepts of pathogenesis and modern approaches to management of systemic sclerosis scleroderma. Systemic sclerosis ssc is an autoimmune inflammatory disorder of unknown etiology characterized by severe and often progressive cutaneous and visceral fibrosis, pronounced alterations in the microvasculature and frequent cellular and humoral immunity abnormalities, as patients with ssc almost universally harbor numerous autoantibodies, some. Emerging role of epigenetics in systemic sclerosis. Derk, md article, author, and disclosure information. Research into ssc has been hampered by its rarity, its clinical. Systemic sclerosis scleroderma, ssc is a heterogeneous autoimmune connective tissue disease of unknown etiology. Identification of a systemic sclerosisprotective sdc2 variant lays the foundation for exploration of the role of syndecan2 in systemic sclerosis in the future. Distler4 the aetiology of ssc is subject to ongoing research, as the precise events that underlie the development of this disease remain unclear. Common symptoms include raynaud phenomenon, polyarthralgia, dysphagia, heartburn, and swelling and eventually. The disease has very limited options with none specifically targeting the fibrotic component, and only in recent times has an insight into the molecular pathways at work come. Systemic sclerosis is an autoimmune connective tissue disease, which is characterised by immune dysregulation and progressive fibrosis that typically affects the skin, with variable internal organ involvement. Systemic sclerosis ssc is a chronic, multisystem connective tissue disease characterized by microangiopathy leading to inflammation and fibrosis involving skin and internal organs.
Systemic sclerosis ssc, also known as scleroderma, is a rare connective tissue disease characterized by vascular and immune dysfunction, leading to fibrosis that can damage multiple organs. Systemic sclerosis ssc, scleroderma is a multisystem connective tissue disorder characterized by immune system activationdysregulation, vasculopathy and progressive fibrosis of the skin and internal organs. Systemic sclerosis merck manuals professional edition. Symptoms may include areas of thickened skin, stiffness, feeling tired, and poor blood flow to the fingers or toes with cold exposure. Systemic sclerosis pathogenesis is blood rheology the key. Novel insights on the role of the innate immune system in systemic sclerosis.
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